Effects of glucose and insulin on fetal glucose oxidation and oxygen consumption

Hay, William W.; DiGiacomo, J. E.; Meznarich, Huei K.; Hirst, Kathryn; Zerbe, Gary O.

doi:10.1152/ajpendo.1989.256.6.e704

Cited by 45 publications

(39 citation statements)

References 13 publications

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“…A similar increase in substrate oxidation has been observed when glucose is infused into the fetus (15). There are likely several mechanisms that explain the lack of increased protein synthesis or accretion in response to a direct amino acid infusion observed in our study.…”

Section: Discussionsupporting

confidence: 84%

Prolonged infusion of amino acids increases leucine oxidation in fetal sheep

Maliszewski

Gadhia

O'Meara

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Maliszewski AM, Gadhia MM, O'Meara MC, Thorn SR, Rozance PJ, Brown LD. Prolonged infusion of amino acids increases leucine oxidation in fetal sheep. Am J Physiol Endocrinol Metab 302: E1483-E1492, 2012. First published March 27, 2012 doi:10.1152/ajpendo.00026.2012.-Maternal high-protein supplements designed to increase birth weight have not been successful. We recently showed that maternal amino acid infusion into pregnant sheep resulted in competitive inhibition of amino acid transport across the placenta and did not increase fetal protein accretion rates. To bypass placental transport, singleton fetal sheep were intravenously infused with an amino acid mixture (AA, n ϭ 8) or saline [control (Con), n ϭ 10] for ϳ12 days during late gestation. Fetal leucine oxidation rate increased in the AA group (3.1 Ϯ 0.5 vs. 1.4 Ϯ 0.6 mol·min Ϫ1 ·kg Ϫ1 , P Ͻ 0.05). Fetal protein accretion (2.6 Ϯ 0.5 and 2.2 Ϯ 0.6 mol·min Ϫ1 ·kg Ϫ1 in AA and Con, respectively), synthesis (6.2 Ϯ 0.8 and 7.0 Ϯ 0.9 mol·min Ϫ1 ·kg Ϫ1 in AA and Con, respectively), and degradation (3.6 Ϯ 0.6 and 4.5 Ϯ 1.0 mol·min Ϫ1 ·kg Ϫ1in AA and Con, respectively) rates were similar between groups. Net fetal glucose uptake decreased in the AA group (2.8 Ϯ 0.4 vs. 3.9 Ϯ 0.1 mg·kg Ϫ1 ·min Ϫ1 , P Ͻ 0.05). The glucose-O2 quotient also decreased over time in the AA group (P Ͻ 0.05). Fetal insulin and IGF-I concentrations did not change. Fetal glucagon increased in the AA group (119 Ϯ 24 vs. 59 Ϯ 9 pg/ml, P Ͻ 0.05), and norepinephrine (NE) also tended to increase in the AA group (785 Ϯ 181 vs. 419 Ϯ 76 pg/ml, P ϭ 0.06). Net fetal glucose uptake rates were inversely proportional to fetal glucagon (r 2 ϭ 0.38, P Ͻ 0.05), cortisol (r 2 ϭ 0.31, P Ͻ 0.05), and NE (r 2 ϭ 0.59, P Ͻ 0.05) concentrations. Expressions of components in the mammalian target of rapamycin signaling pathway in fetal skeletal muscle were similar between groups. In summary, prolonged infusion of amino acids directly into normally growing fetal sheep increased leucine oxidation. Amino acid-stimulated increases in fetal glucagon, cortisol, and NE may contribute to a shift in substrate oxidation by the fetus from glucose to amino acids. pregnancy; insulin; fetal protein metabolism; fetal growth PREVIOUS ATTEMPTS TO IMPROVE fetal outcomes with use of maternal high-protein supplementation have actually increased the risk for small-for-gestational-age birth and infant mortality (26,36). Similarly, supplementation of pregnant sheep with intravenous amino acids for several days at the end of gestation demonstrated adverse fetal effects, including hypoxia and respiratory and metabolic acidosis (34). The mechanisms that explain poor fetal outcomes in response to maternal protein supplementation during pregnancy are unknown.Experiments using normal pregnant sheep have led to some testable explanations for how high-protein supplementation during pregnancy might adversely affect fetal outcomes (4). Short-and long-term maternal amino acid infusions using mixtures of amino acids with a higher essential-nonessential ...

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Section: Discussionsupporting

confidence: 84%

Prolonged infusion of amino acids increases leucine oxidation in fetal sheep

Maliszewski

Gadhia

O'Meara

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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“…The relative proportion of glucose oxidized during short-term, 3-4 h studies (about 55% in foetal sheep) does not change significantly over the physiological range of foetal glucose utilization rates, indicating little or no effect of glucose or insulin on the intracellular pathways of glucose metabolism, at least in the foetus as a whole; though individual tissues and their unique cellular metabolic pathways may vary significantly in their responsiveness to glucose and insulin. Similar observations have been made for foetal metabolic rates, measured as net foetal oxygen uptake rates via the umbilical circulation, which remain relatively constant (± 5%) over the entire physiological range of oxygen supply and blood oxygen content, despite marked reductions or increases in glucose supplies (Hay et al, 1989).…”

Section: Foetal Growthsupporting

confidence: 77%

Foetal and neonatal energy metabolism in pigs and humans: a review

Mota-Rojas¹,

Orozco-Gregorio²,

Villanueva-García³

et al. 2011

Vet. Med. - Czech

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ABSTRACT:The aim of this review was to elaborate a conceptual framework of the most important aspects of the main biochemical processes of synthesis and breakdown of energy substrates that human and pig foetuses and newborns can use during the transition from foetus to newborn. Under normal physiological conditions, the growth and development of the foetus depends upon nutrients such as glucose, lipids and amino acids. In addition to the maternal and foetal status, genetic factors are also reported to play a role. The main function of the placenta in all species is to promote the selective transport of nutrients and waste products between mother and foetus. This transport is facilitated by the close proximity of the maternal and foetal vascular systems in the placenta. The foetus depends on the placental supply of nutrients, which regulates energy reserves by means of glycogen storage. Also, the synthesis of foetal hepatic glycogen guarantees energy reserves during perinatal asphyxia or maternal hypoglycaemia. However, the foetus can also obtain energy from other resources, such as gluconeogenesis from the intermediary metabolism of the Krebs cycle and most amino acids. Later, when the placental glucose contribution ends during the transition to the postnatal period, the maturation of biological systems and essential metabolic adaptations for survival and growth is required. The maintenance of normoglycaemia depends on the conditions that determine nutrient status throughout life: the adequacy of glycogen stores, the maturation of the glycogenolytic and gluconeogenic pathway, and an integrated endocrine response.

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“…In contrast to findings in the fetal foal and lamb (Hay, Meznarich, DiGiacomo, Hirst & Zerbe, 1988;Hay et al 1989;Fowden & Silver, 1995 a, b), there was no relationship between the rate of glucose utilization and the glucose concentration in the fetal pig in the present study.…”

Section: Discussioncontrasting

confidence: 99%

“…The rates of uptake and utilization of glucose, and of CO2 production from glucose carbon, by the fetal piglet were significantly higher than the corresponding values in the fetal lamb at the equivalent stage of gestation but were similar to those measured in the fetal foal using identical methodology in the same laboratory (Table 3). The mean rates of glucose metabolism found in the fetal pig in the present study were also higher than the range of mean values for umbilical glucose uptake (17.2-33 1 4umol min-1 kg-1), glucose utilization (25.8-38-1 ,umol min-' kg-1) and CO2 production from glucose carbon (81 2-91-7 jtmol min-' kg-') observed previously in fetal sheep under similar conditions in other laboratories (Hay et al 1983;Bloch, Menon & Sperling, 1988;Owens, Falconer & Robinson, 1989;Hay, DiGiacomo, Meznarich, Hirst & Zerbe, 1989). The weight-specific rate of umbilical 02 uptake in the fetal pig was at the upper end of the range of values observed in fetal sheep (295-340 #rmol min-m kg-') but was 10-15 % higher than the value observed in fetal foals at a similar stage of gestation (Hay et al 1983(Hay et al , 1989Owens, 1991;Thureen, Trembler, Meschia, Makowski & Wilkening, 1992;Fowden & Silver, 1995 a, b).…”

Section: Discussionsupporting

confidence: 53%

Glucose, lactate and oxygen metabolism in the fetal pig during late gestation

Fowden¹,

Forhead²,

Silver³

et al. 1997

Experimental Physiology

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SUMMARYUsing [U-_4C]glucose tracer, rates of umbilical uptake, utilization and production of glucose, and of CO2 production from glucose carbon, were measured in seven chronically catheterized fetal pigs, when the sow was in the fed state, between 100 and 113 days of gestation (term, 114 + 2 days). At the same time, rates of umbilical 02 and lactate uptake were determined in all seven fetuses by the Fick principle. The mean fetal rates of umbilical glucose uptake, glucose utilization and CO2 production from glucose carbon were 38.4 + 4.2, 41-3 + 5.2 and 126-9 + 12-6 #smol min-' (kg fetal body weight)-', respectively (n = 7). No glucose production was therefore detected in the fetuses. Production of CO2 from glucose carbon accounted for 37-3 + 3.4% (n =7) of the umbilical 02 uptake, which averaged 340 + 13 jumol min-kg-' (n = 7). There was also significant umbilical lactate uptake in the fetal piglets when the sow was in the fed state (32.6 + 10-4 #tsmol min-1 kg-', n = 7, P <0-05). No significant changes in fetal glucose, 0°or lactate metabolism were observed with increasing age towards term. The fetal rates of glucose metabolism and of umbilical uptake of 02 and lactate were not correlated with the fetal blood glucose level. Hence, glucose is used for both oxidative and tfOn-oxidative metabolism in utero and is an important, although not the sole, source of carbon for metabolic processes in the fetal pig during late gestation.

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Effects of glucose and insulin on fetal glucose oxidation and oxygen consumption

Cited by 45 publications

References 13 publications

Prolonged infusion of amino acids increases leucine oxidation in fetal sheep

Prolonged infusion of amino acids increases leucine oxidation in fetal sheep

Foetal and neonatal energy metabolism in pigs and humans: a review

Glucose, lactate and oxygen metabolism in the fetal pig during late gestation

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